Abstract/Project Summary: Project #3 In addicted individuals, exposure to conditioned drug cues (e.g., paraphernalia) elicits craving: the desire to use drugs1. Craving is increasingly recognized as an important contributory factor in addiction in general, and in cigarette smoking in particular2-7. Indeed, it has been shown to predict smoking and relapse following abstinence8-16, suggesting that treatments to mitigate the effects of cue-induced craving are needed17. Consistently, skills training in regulation of craving (a form of cognitive control) is an important feature of many interventions7, 18-22, including cognitive-behavioral therapy23, 24 and mindfulness-based treatments25, 26. Craving and its regulation have distinct neurobiological mechanisms. The neural correlates of craving include the ventral striatum and ventromedial prefrontal cortex27-29. We developed the Regulation of Craving (ROC) task30-35 to investigate the neural mechanisms associated with the regulation of craving. In this task, nicotine-dependent smokers are exposed to smoking-related stimuli. In one condition they experience craving, and in another (the regulation condition), they are instructed to use a strategy to modulate their craving for cigarettes31. Research has shown that self-reported craving and craving-related neural activity are significantly reduced during the regulation condition32, 34, 36. However, the exact neural mechanisms by which regulation operates depend on the strategy used. Specifically, regulation of craving with cognitive strategies depends on activation in prefrontal regions, typically associated with cognitive control, such as dorsolateral and ventrolateral prefrontal cortex32, 36-38. However, regulation with mindfulness strategies does not involve PFC34. We propose that brief training in regulation of craving may increase the efficacy of smoking cessation treatments, but that training in cognitive vs. mindfulness-based strategies may operate via different psychological and neural mechanisms. We propose to test the efficacy of such training by randomizing 126 cigarette smokers to the following conditions: 1) brief training in cognitive regulation of craving + standard treatment, 2) mindfulness-based training + standard treatment, and 3) standard treatment (no training). Training will be delivered in 4x1 hour computerized sessions over four weeks, with an 8-week follow-up. We will evaluate the effects of training on craving and regulation of craving measured by self-report and functional magnetic resonance imaging during the ROC task administered pre- and post- treatment, as well as smoking. This project promises to advance our psychological and neurobiological understanding of craving and its regulation, how these processes change during specific types of training, and how they relate to actual smoking behaviors. Results from this study hold potential to allow neurobiologically-targeted adaptation of current treatments, with an aim of discovering potentially precise biological predictions of treatment outcomes.